Overview of LRRK2 and its substrates in vesicle or membrane trafficking. (Top) Schematic representation of LRRK2 domains, including armadillo repeats (ARM), ankyrin repeats (ANK), leucine-rich repeats (LRR), a ROC domain, a COR domain, a kinase domain, and a C-terminal WD40 domain. Pathogenic mutations are indicated above. (Bottom) Two categories of LRRK2 substrates discussed in this review. LRRK2 phosphorylates a subset of Rab GTPases, master regulators of vesicle trafficking (left), and key molecules of synaptic transmission (right).